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Over the past three decades, congenital toxoplasmosis in the U.S. arose from two specific subtypes of Toxoplasma gondii and both improved with treatment, data from a collaborative study showed.

Serotyping of almost 200 congenitally infected patients showed that serotype II and serotypes not exclusively II (NE-II) accounted for similar proportions of infection from 1981 to 2009. The NE-II serotype had associations with certain demographic factors, geographic areas, prematurity, and severe disease.

Treatment with pyrimethamine (Daraprim) and sulfadizine, regardless of dosage, led to improved outcomes relative to historical data for untreated patients, according to an article published online in Clinical Infectious Diseases.

"NE-II serotypes are more often present than serotype II in infants born prematurely or with severe disease, and in certain demographics," Rima McLeod, MD, of the University of Chicago, and coauthors wrote. "Outcomes following treatment were independent of parasite allelic type and emphasize the need to identify all patients, as they will benefit from treatment."

When unrecognized at birth, congenital toxoplasmosis causes cognitive and motor dysfunction and seizures later in life. Untreated infection with T. gondii leads to eye disease in adolescence in 80% to 90% of cases, the authors noted.

In animal models and tissue culture, different T. gondii genotypes behave differently. Type I parasites are more virulent and more likely to cause death in animals. Type II parasites are less lethal in mice but cause brain cysts and grow more slowly culture. Type III parasites have intermediate characteristics.

Few studies have examined parasite distribution in the U.S. Development of an enzyme-linked immunosorbent assay (ELISA) has enabled discrimination of infection by type II and non-II parasites. Using ELISA results, the authors examined parasite distribution in two well-defined cohorts of patients with congenital toxoplasmosis.

Investigators in the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) have followed two cohorts of patients with congenital toxoplasmosis since 1981. One cohort consists of patients who had diagnoses as newborns and treatment within the first year of life. The second cohort consists of patients whose diagnosis occurred after age 1.

For the study. investigators obtained sera from 183 mothers who transmitted T. gondii to their fetuses, 151 infants with substantial disease burden at diagnosis during the newborn period, and 42 patients referred to the NCCCT for evaluation after the first year of life.

The NE-II strain accounted for 61% of infections, which differed significantly (P<0.001) from cohorts studied in France (84% type II) and Brazil (100% NE-II). The distribution of II and NE-II did not differ between patients whose diagnoses occurred in the perinatal period versus those whose diagnoses occurred later.

Serotypes II and NE-II were diagnosed throughout the U.S., but the NE-II serotype predominated in hot, humid climate (P=0.02) and in rural areas (P<0.01). NE-II also was associated with lower socioeconomic status (P<0.001), Hispanic ethnicity (P<0.001), prematurity (P=0.03), severe disease at birth (P<0.01), and maternal illness during pregnancy (P=0.02).

More patients with serotype II infection had susceptibility alleles (P=0.04).

Regardless of serotype, treatment was associated with improved outcomes compared with historical data for untreated patients. Significant differences for one or both serotypes emerged for the following:

• Vision <20/30, NE-II only (P<0.01)
• New eye lesions (P<0.01)
• Motor/tone abnormalities (P<0.01)
• IQ <70 (P<0.01)
• Decrease in IQ ≥15 (P<0.01)
• Hearing loss >30 db, NE-II only (P<0.01)

The study had some limitations. Although they results were "robust," the authors acknowledged that current serotyping methods have limitations, such as pinpointing cases of human toxoplasmosis caused by a new parasite lineage called type X.

Also, associations between serotypes and pheontypes could be related to factors that influence acquisition earlier in gestation when fetal infection is most severe. "For example, NE-II parasites might be preferentially transmitted earlier," they said.

Nonetheless, this well-characterized NCCCTS cohort will be valuable for future studies and as additional typing reagents and approaches become available, they concluded.

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